HIF1-driven transcriptional changes in the heart

Ischemic heart disease is a leading cause of heart failure and hypoxia inducible factor 1 (HIF1) has been shown to be a key transcription factor in the early response to hypoxic injury. We previously developed an inducble model of cardiomyopathy using cardiomyocyte-specific expression of a mutated, oxygen-stable form of HIF-1? (HIF-PPN). In this study, we used high throughput sequencing to explore HIF1-mediated transcriptional changes in the heart. Overall design: Male mice expressing a stable form of HIF-1a under control of the Tet-Off system were given water either containing doxycycline (ON) or after withdrawal from doxycycline for three days (3D). Control mice remained on doxycycline and while those off doxycycline expressed HIF-PPN. Hearts were isolated and flash frozen before RNA isolation. Three mice were used for each condition as biological replicates.